Investigations from this laboratory have shown that permanent destruction of the sympathetic ganglia is obtained by injecting newborn mammals with an antiserum to the Nerve Growth Factor (Immunosympathectomy) and by 6-hydroxydopamine (chemical sympathectomy). It is the object of this research project to analyze on a comparative basis the effects of agents which interfere with sympathetic function on growth and development of adrenergic neurons. To this aim, drugs which block adrenergic transmission (such as guanethidine, bretylium, rauwolfian alkaloids, bethanidine, guanoxan) and agents which inhibit the synthesis of the neurotransmitter, will be injected into newborn mammals. The analysis of the possible morphogenetic effects of these agents on sympathetic neurons will be carried out at the structural, ultrastructural, biochemical and pharmacological levels. These studies will be extended also to adrenergic neurons located in the central nervous system. Interreaction between the nerve growth factor and agents which interfere with sympathetic function will be studied in vivo and in vitro. Experiments in vitro will be performed on sympathetic ganglia of chick embryos cultured in semisolid and liquid media in presence of the isotopic labelled agents. In vitro studies also will be carried out on human and murine neuroblastomas. The degree of functional impairment of the sympathetic nervous system found in the different models of sympathectomy will be compared by monitoring the response of sympathectomized and normal animals to cold and hemorrhage. The possibility of vascular supersensitivity in sympathectomized animals will be explored.